Previously we have shown loss of heterozygosity (LOH) on chromosome 17q21 in 30% of primary human breast tumors using seventeen polymorphic sequences tagged site markers. Deletions of this region have a significant correlation with the clinical parameters of aggressive breast cancer. The hereditary breast cancer gene BRCA1 has previously been localized to chromosome 17q21. This gene, however, is not the target for LOH sporadic breast cancer. The smallest common region deleted occurred in an interval between the 17S846 and 17S746 polymorphic markers. These loci are located between two recombinant P1 bacteriophage clones: 122F4 and 50H1. To identify the target gene for LOH, we defined the map of this region. The 5' end of 122F4 contains the human Plakoglobin gene. The human homologue of mouse FK506BP gene, FLJ22041, is located further down 122F4 and in the opposite transcriptional orientation. This gene, spanning 12 Kb contains 11 exons, which encodes a 2.2 Kb RNA species that is expressed in the normal mammary gland. On 122F4 we also found the 5' end of Sc65 that encodes for an autonuclear protein and is expressed in the normal mammary gland and the 3'end of an unknown gene which correspond to the R61279 human EST, weakly similar to human AF151067. After screening a P1 library using the 5' portion of this gene as a probe, we found another P1 phage clone, 23877 containing the complete gene. R61279 spans in a region of 15.5 Kb and consists of 8 exons It is located approximately 1.500 kb down in opposite transcriptional orientation to hFKBP. On 23877 P1 phage we also found the full length of SC65 and the FLJ10572 gene. PCR amplification of all the genes contained on 122 F4 and 23877 P1-phage showed that no one of these genes are located on 50H1 p1 phage. Nucleotide sequence of 50H1p1 phage contains Gastrin (GAS) and neuroan-1 genes. The latter gene encodes a protein that is related to the Hap1 protein (Huntington protein). Neither of these genes is expressed in normal mammary tissue. Using nucleotide sequence analysis or SSCP analysis we have not detected any mutations in the Plakoglobin,, hFKBP656 , R61279 and hSC65 genes in tumors having LOH at 17q21.